{"id":{"repo_id":"auckland-ms","oai_identifier":"oai:researchspace.auckland.ac.nz:2292/73549"},"canonical_url":"https://search.dev.ndltd.org/etd/auckland-ms/oai:researchspace.auckland.ac.nz:2292/73549","repository":{"repo_id":"auckland-ms","name":"University of Auckland","base_url":"https://researchspace.auckland.ac.nz/server/oai/request"},"display":{"title":"Exploring the Effects of Adjuvant Selection on a Novel Polyvalent Staphylococcus aureus Vaccine","abstract":"Staphylococcus aureus is an important human pathogen that causes a wide range of morbidities, from superficial skin infections to severe and potentially lethal conditions like sepsis. The emergence of multi-drug-resistant strains and the subsequent reduction in effective antibiotic options underscore the necessity for alternative treatments, such as vaccines. This project explored the optimisation of a novel polyvalent S. aureus protein vaccine based on three highly conserved proteins from the staphylococcal superantigen-like (SSL) family: SSL3, SSL7 and SSL11. These proteins are immune evasion factors and target different aspects of the host's immune response. The novel vaccine candidate, polySSL, was expressed as a single fusion protein, and the efficacy was evaluated using an intraperitoneal murine infection model. Alternative orders for the polySSL were investigated, but a particular focus was on optimal adjuvant selection for enhanced immunogenicity. Immunisation with the polySSL in any order combined with the adjuvant AddaVax resulted in the production of antigen-specific IgG titres against each vaccine component with some neutralising capability and a reduction in S. aureus burden. Minor variations were observed between protein orders, but significant differences were observed in a pilot study exploring the addition of different pattern recognition receptor agonists combined with the adjuvant AdjuPhos. The addition of toll-like receptor 2 (TLR2)-containing agonists enhanced S. aureus clearance, and consequently, further cellular studies were undertaken with a novel TLR2 agonist to identify the protective host response. The splenocyte supernatant of mice immunised with the polySSL-TLR2 combination had increased production of the cytokines IFN-γ, TNF, and IL-6 following antigen-specific stimulation. Following S. aureus challenge, polySSL-vaccinated mice had higher proportions of CD4+ effector memory T cells. The use of the TLR2 agonist as a mucosal pretreatment for S. aureus was also evaluated using a murine colonisation model, which produced a localised inflammatory response with increased TNF and IL-1α but was ineffective at bacterial clearance. These results demonstrated the importance of adjuvant selection, and some insight was gained into desirable immune profiles. TLR2 agonists were highlighted as drivers of a protective S. aureus response when combined with the polySSL vaccine candidate. This promising S. aureus vaccine candidate warrants further investigation.","abstract_html":"Staphylococcus aureus is an important human pathogen that causes a wide range of morbidities, from superficial skin infections to severe and potentially lethal conditions like sepsis. The emergence of multi-drug-resistant strains and the subsequent reduction in effective antibiotic options underscore the necessity for alternative treatments, such as vaccines. This project explored the optimisation of a novel polyvalent S. aureus protein vaccine based on three highly conserved proteins from the staphylococcal superantigen-like (SSL) family: SSL3, SSL7 and SSL11. These proteins are immune evasion factors and target different aspects of the host's immune response. The novel vaccine candidate, polySSL, was expressed as a single fusion protein, and the efficacy was evaluated using an intraperitoneal murine infection model. Alternative orders for the polySSL were investigated, but a particular focus was on optimal adjuvant selection for enhanced immunogenicity. Immunisation with the polySSL in any order combined with the adjuvant AddaVax resulted in the production of antigen-specific IgG titres against each vaccine component with some neutralising capability and a reduction in S. aureus burden. Minor variations were observed between protein orders, but significant differences were observed in a pilot study exploring the addition of different pattern recognition receptor agonists combined with the adjuvant AdjuPhos. The addition of toll-like receptor 2 (TLR2)-containing agonists enhanced S. aureus clearance, and consequently, further cellular studies were undertaken with a novel TLR2 agonist to identify the protective host response. The splenocyte supernatant of mice immunised with the polySSL-TLR2 combination had increased production of the cytokines IFN-γ, TNF, and IL-6 following antigen-specific stimulation. Following S. aureus challenge, polySSL-vaccinated mice had higher proportions of CD4+ effector memory T cells. The use of the TLR2 agonist as a mucosal pretreatment for S. aureus was also evaluated using a murine colonisation model, which produced a localised inflammatory response with increased TNF and IL-1α but was ineffective at bacterial clearance. These results demonstrated the importance of adjuvant selection, and some insight was gained into desirable immune profiles. TLR2 agonists were highlighted as drivers of a protective S. aureus response when combined with the polySSL vaccine candidate. This promising S. aureus vaccine candidate warrants further investigation.","abstract_has_math":false,"creators":["Peterken, Kelly Pania"],"institution":"ResearchSpace@Auckland","degree_name":"PhD","degree_level":"Doctoral","degree_discipline":"Biomedical Science","degree_department":null,"school":null,"contributors":[],"advisors":["Radcliff, Fiona","Fraser, John"],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-09-17","date_published":"2025-09-17","updated_at":"2026-07-24T01:04:34Z","subjects":["vaccine","adjuvant","staphylococcus","aureus"],"languages":[],"rights":["Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated."],"rights_urls":["https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm"],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2292/73549","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Radcliff, Fiona","Fraser, John"]},{"key":"dc:creator","label":"Author","values":["Peterken, Kelly Pania"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-09-17T20:14:31Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-09-17T20:14:31Z"]},{"key":"dc:date.issued","label":"Date","values":["2025-09-17"]},{"key":"dc:publisher","label":"Institution","values":["ResearchSpace@Auckland"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Science"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["PhD"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Auckland"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["vaccine","adjuvant","staphylococcus","aureus"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated."]},{"key":"dc:rights.uri","label":"Rights URI","values":["https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/2292/73549"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Staphylococcus aureus is an important human pathogen that causes a wide range of morbidities, from superficial skin infections to severe and potentially lethal conditions like sepsis. The emergence of multi-drug-resistant strains and the subsequent reduction in effective antibiotic options underscore the necessity for alternative treatments, such as vaccines. This project explored the optimisation of a novel polyvalent S. aureus protein vaccine based on three highly conserved proteins from the staphylococcal superantigen-like (SSL) family: SSL3, SSL7 and SSL11. These proteins are immune evasion factors and target different aspects of the host's immune response. The novel vaccine candidate, polySSL, was expressed as a single fusion protein, and the efficacy was evaluated using an intraperitoneal murine infection model. Alternative orders for the polySSL were investigated, but a particular focus was on optimal adjuvant selection for enhanced immunogenicity. Immunisation with the polySSL in any order combined with the adjuvant AddaVax resulted in the production of antigen-specific IgG titres against each vaccine component with some neutralising capability and a reduction in S. aureus burden. Minor variations were observed between protein orders, but significant differences were observed in a pilot study exploring the addition of different pattern recognition receptor agonists combined with the adjuvant AdjuPhos. The addition of toll-like receptor 2 (TLR2)-containing agonists enhanced S. aureus clearance, and consequently, further cellular studies were undertaken with a novel TLR2 agonist to identify the protective host response. The splenocyte supernatant of mice immunised with the polySSL-TLR2 combination had increased production of the cytokines IFN-γ, TNF, and IL-6 following antigen-specific stimulation. Following S. aureus challenge, polySSL-vaccinated mice had higher proportions of CD4+ effector memory T cells. The use of the TLR2 agonist as a mucosal pretreatment for S. aureus was also evaluated using a murine colonisation model, which produced a localised inflammatory response with increased TNF and IL-1α but was ineffective at bacterial clearance. These results demonstrated the importance of adjuvant selection, and some insight was gained into desirable immune profiles. TLR2 agonists were highlighted as drivers of a protective S. aureus response when combined with the polySSL vaccine candidate. This promising S. aureus vaccine candidate warrants further investigation."]},{"key":"dc:title","label":"Title","values":["Exploring the Effects of Adjuvant Selection on a Novel Polyvalent Staphylococcus aureus Vaccine"]}]}],"canonical_facts":{"dc:contributor.advisor":["Radcliff, Fiona","Fraser, John"],"dc:creator":["Peterken, Kelly Pania"],"dc:date.accessioned":["2025-09-17T20:14:31Z"],"dc:date.available":["2025-09-17T20:14:31Z"],"dc:date.issued":["2025-09-17"],"dc:description.abstract":["Staphylococcus aureus is an important human pathogen that causes a wide range of morbidities, from superficial skin infections to severe and potentially lethal conditions like sepsis. The emergence of multi-drug-resistant strains and the subsequent reduction in effective antibiotic options underscore the necessity for alternative treatments, such as vaccines. This project explored the optimisation of a novel polyvalent S. aureus protein vaccine based on three highly conserved proteins from the staphylococcal superantigen-like (SSL) family: SSL3, SSL7 and SSL11. These proteins are immune evasion factors and target different aspects of the host's immune response. The novel vaccine candidate, polySSL, was expressed as a single fusion protein, and the efficacy was evaluated using an intraperitoneal murine infection model. Alternative orders for the polySSL were investigated, but a particular focus was on optimal adjuvant selection for enhanced immunogenicity. Immunisation with the polySSL in any order combined with the adjuvant AddaVax resulted in the production of antigen-specific IgG titres against each vaccine component with some neutralising capability and a reduction in S. aureus burden. Minor variations were observed between protein orders, but significant differences were observed in a pilot study exploring the addition of different pattern recognition receptor agonists combined with the adjuvant AdjuPhos. The addition of toll-like receptor 2 (TLR2)-containing agonists enhanced S. aureus clearance, and consequently, further cellular studies were undertaken with a novel TLR2 agonist to identify the protective host response. The splenocyte supernatant of mice immunised with the polySSL-TLR2 combination had increased production of the cytokines IFN-γ, TNF, and IL-6 following antigen-specific stimulation. Following S. aureus challenge, polySSL-vaccinated mice had higher proportions of CD4+ effector memory T cells. The use of the TLR2 agonist as a mucosal pretreatment for S. aureus was also evaluated using a murine colonisation model, which produced a localised inflammatory response with increased TNF and IL-1α but was ineffective at bacterial clearance. These results demonstrated the importance of adjuvant selection, and some insight was gained into desirable immune profiles. TLR2 agonists were highlighted as drivers of a protective S. aureus response when combined with the polySSL vaccine candidate. This promising S. aureus vaccine candidate warrants further investigation."],"dc:identifier.uri":["https://hdl.handle.net/2292/73549"],"dc:publisher":["ResearchSpace@Auckland"],"dc:rights":["Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated."],"dc:rights.uri":["https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm"],"dc:subject":["vaccine","adjuvant","staphylococcus","aureus"],"dc:title":["Exploring the Effects of Adjuvant Selection on a Novel Polyvalent Staphylococcus aureus Vaccine"],"dc:type":["Thesis"],"thesis:degree_discipline":["Biomedical Science"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["PhD"],"thesis:institution_name":["The University of Auckland"]},"updated_at":"2026-07-24T01:04:34Z"}